A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors

Author:

Fenniche Salma1234,Oukabli Mohamed56,Oubaddou Yassire1ORCID,Chahdi Hafsa56,Damiri Amal56,Alghuzlan Abir24ORCID,Laraqui Abdelilah5,Dakka Nadia1,Bakri Youssef1,Dupuy Corinne234,Ameziane El Hassani Rabii1ORCID

Affiliation:

1. Laboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, Morocco

2. Gustave Roussy Cancer Campus, Pavillon de Recherche N°2, F-94805 Villejuif, France

3. Faculty of Medicine and Pharmacy, University Paris-Saclay, F-91400 Orsay, France

4. Unité Mixte de Recherche UMR9019 Centre National de la Recherche Scientifique, Pavillon de Recherche N°2, F-94805 Villejuif, France

5. Service of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Rabat 1014, Morocco

6. Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10001, Morocco

Abstract

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAFV600E tumors compared to PTC-BRAFwt tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves’ disease, ten goiters, and 20 hyperplasias). We detected the BRAFV600E mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAFV600E expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAFV600E mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations.

Funder

Cancer Research Institute

PHC TOUBKAL

Agence Nationale Des Plantes Médicinales Et Aromatiques

CNRST, Maroc

Publisher

MDPI AG

Subject

Microbiology (medical),Molecular Biology,General Medicine,Microbiology

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